Proposed Mechanism of Action

PRO-DENSE® Bone Graft SubstituteDense, Direct Bone Deposition

PRO-DENSE® Bone Graft Substitute has a triphasic resorption profile that provides an ideal environment for the direct deposition of bone by binding growth factors† and by providing a slow re-sorbing matrix that supports healing across the defect.

The following illustrations describe the basic steps in the process of new bone formation.

Proposed Mechanism of Action
1. Angiogenesis is a key early event. The CaSO4 of the implant resorbs first, revealing a porous calcium phosphate scaffold conducive to vascular infiltration.
2. The resulting brushite/TCP scaffold with interconnecting pores binds free proteins such as VEGF and BMP-2 at the implant/defect interface.†
3. Resorption of the PRO-DENSE® scaffold releases bound proteins. Active proteins recruit cells to the implant surface.†
4. Growth factors in the implant/defect interface region, including BMPs, stimulate proliferation and differentiation of mesenchymal stem cells.
5. Differentiated osteoblasts lay down osteoid which then mineralizes to become newly woven bone.
6. The principles of Wolff’s Law drive remodeling.

†Growth factor binding based on in vitro data of BMP-2 and VEGF. Data on file.

FASTER THAN AUTOGRAFT*: The accelerated rate of healing of the PRO-DENSE® graft treated defects compared to those treated with autograft is principally evident by the higher density bone (i.e., 170% average increase in area fraction of new bone compared to autograft at 13 weeks) and superior average mechanical properties at 13 weeks.

DENSER THAN AUTOGRAFT*: Histomorphometry reveals that the amount of newly regenerated bone of the PRO-DENSE® injectable graft treated defects at 13 weeks demonstrated a statistically significant 170% average increase in new bone formation versus defects treated with autograft. PRO-DENSE® injectable graft new bone area fraction is on average 170% denser than autograft at 13 weeks.

*All claims are based on a critically sized canine proximal humerus defect model. It is unknown how results from the canine model compare with clinical results in humans.